Mitochondria uncoupling by a long chain fatty acyl analogue.
Mitochondria uncoupling by fatty acids in vivo is still questionable, being confounded by their dual role as substrates for oxidation and as putative genuine uncouplers of oxidative phosphorylation. To dissociate between substrate and the uncoupling activity of fatty acids in oxidative phosphorylation, the uncoupling effect was studied here using a nonmetabolizable long chain fatty acyl analogue. beta,beta'-Methyl-substituted hexadecane alpha,omega-dioic acid (MEDICA 16) is reported here to induce in freshly isolated liver cells a saturable oligomycin-insensitive decrease in mitochondrial proton motive force with a concomitant increase in cellular respiration. Similarly, MEDICA 16 induced a saturable decrease in membrane potential, proton gradient, and proton motive force in isolated liver and heart mitochondria accompanied by an increase in mitochondrial respiration. Uncoupling by MEDICA 16 in isolated mitochondria was partially suppressed by added atractyloside. Hence, fatty acids may act as genuine uncouplers of cellular oxidative phosphorylation by interacting with specific mitochondrial proteins, including the adenine nucleotide translocase.
Hermesh
O
O
Department of Human Nutrition and Metabolism, Faculty of Medicine, Hebrew University, P. O. Box 12272, Jerusalem 91120, Israel.
Kalderon
B
B
Bar-Tana
J
J
D000818:Animals; D001278:Atractyloside / Q000494:pharmacology; D019069:Cell Respiration / Q000187:drug effects; D002478:Cells, Cultured; D005227:Fatty Acids / Q000494:pharmacology; D005434:Flow Cytometry; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology; D010169:Palmitic Acids / Q000494:pharmacology*; D051381:Rats; D014475:Uncoupling Agents / Q000494:pharmacology*
D005227:Fatty Acids; D009840:Oligomycins; D010169:Palmitic Acids; D014475:Uncoupling Agents; D001278:Atractyloside; D019308:Palmitic Acid; C056166:MEDICA 16; D000226:Mitochondrial ADP, ATP Translocases; D010100:Oxygen